Approximately 5% of all breast cancers can be attributed to an inherited mutation in one of two cancer susceptibility genes, BRCA1 and BRCA2. We searched for genes that have the potential to distinguish healthy BRCA1 and BRCA2 mutation carriers from non-carriers based on differences in expression profiling. Using expression microarrays we compared gene expression of irradiated lymphocytes from BRCA1 and BRCA2 mutation carriers versus control non-carriers. We identified 137 probe sets in BRCA1 carriers and 1345 in BRCA2 carriers with differential gene expression. Gene Ontology analysis revealed that most of these genes relate to regulation pathways of DNA repair processes, cell cycle regulation and apoptosis. Real-time PCR was performed on the 36 genes which were most prominently differentially expressed in the microarray assay; 21 genes were shown to be significantly differentially expressed in BRCA1 or BRCA2 mutation carriers as compared to controls (p<0.05). Based on a validation study with 40 mutation carriers and 17 non-carriers, a multiplex model that included six or more coincidental genes of 18 selected genes was constructed in order to predict the risk of carrying a mutation. The results using this model showed sensitivity 95% and specificity 88%. In summary, our study provides insight into the biological effect of heterozygous mutations in BRCA1 and BRCA2 genes in response to ionizing irradiation induced DNA damage. We also suggest a set of 18 genes that can be used as a prediction and screening tool for BRCA1 or BRCA2 mutational carriers by using easily obtained lymphocytes.
Determination of molecular markers for BRCA1 and BRCA2 heterozygosity using gene expression profiling.
Specimen part
View SamplesRNA sequencing of T-ALL tumors derived from genetically modified mouse models: CIC loss-of-function, HRASG12V driven from the Kras promoter and Trp53 KO. Results provide insight into the role of the RAS/CIC axis in T-ALL development. Overall design: RNA-Sequencing of 5 CIC LOF, 3 K:HrasG12V and 4 Trp53 KO T-ALL murine tumor samples.
Inactivation of Capicua in adult mice causes T-cell lymphoblastic lymphoma.
Cell line, Treatment, Subject
View SamplesLung cancers exhibit pronounced functional heterogeneity, confounding precision medicine. We studied how the cell-of-origin contributes to phenotypic heterogeneity following conditional expression of KrasG12D and loss of Lkb1 (Kras;Lkb1). Using progenitor cell type-restricted adenoviral-Cre to target cells expressing Surfactant Protein C (SPC) or club cell antigen 10 (CC10), we show that Ad5-CC10-Cre infected mice exhibit a shorter latency compared with Ad5-SPC-Cre cohorts. We further demonstrate that CC10+ cells are the predominant progenitors of adenosquamous carcinoma (ASC) tumors, and give rise to a wider spectrum of histotypes that includes mucinous and acinar adenocarcinomas. Transcriptome analysis shows ASC histotype-specific upregulation of proinflammatory and immunomodulatory genes. This is accompanied with an ASC-specific immunosuppressive environment, consisting of downregulated MHC genes, recruitment of CD11b+ Gr-1+ tumor-associated neutrophils (TANs) and decreased T-cell numbers. We conclude that progenitor cell-specific etiology influences the Kras;Lkb1-driven tumor histopathology spectrum and histotype-specific immune microenvironment.
Cell of Origin Links Histotype Spectrum to Immune Microenvironment Diversity in Non-small-Cell Lung Cancer Driven by Mutant Kras and Loss of Lkb1.
Specimen part
View SamplesTo characterize genes, pathways, and transcriptional regulators enriched in the mouse cornea, we compared the expression profiles of whole mouse cornea, bladder, esophagus, lung, proximal small intestine, skin, stomach, and trachea.
The Ets transcription factor EHF as a regulator of cornea epithelial cell identity.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The Ets transcription factor EHF as a regulator of cornea epithelial cell identity.
Age, Specimen part
View SamplesWhile the mouse cornea has been well characterized morphologically, the transcriptional changes have not been described in detail. To characterize the genes, pathways, and transcriptional regulators involved in mouse cornea development and aging, we isolated whole cornea from wildtype CB6 mice at several developmental timepoints and every 6 months in the adult. Corneal epithelium and stroma were isolated at one timepoint to provide insights into the genes that are unique to each tissue.
The Ets transcription factor EHF as a regulator of cornea epithelial cell identity.
Age, Specimen part
View SamplesStabilin-1/CLEVER-1 is a multidomain protein present in lymphatic and vascular endothelial cells and in M2 immunosuppressive macrophages. Stabilin-1 functions in scavenging, endocytosis and leukocyte adhesion to and transmigration through the endothelial cells. We have analyzed the putative functions of Stabilin-1 in blood monocytes and found that in healthy individuals 60-80% of both CD14+CD16- and CD14+C16+ monocytes, but not CD14dimCD16+ monocytes, expressed Stabilin-1 on the surface. Microarray and RNAseq analysis was performed to get more insight into the effect of Stabilin-1 expression on human monocytes transcriptome. Overall design: The transcriptome of human monocytes transfected with Stabilin-1 siRNA was compared to that of control siRNA transfected monocytes
Monocyte Stabilin-1 Suppresses the Activation of Th1 Lymphocytes.
No sample metadata fields
View Samplesaffy_seed_kinetic_wheat - affy_seed_kinetic_wheat - Study gene expression during the grain developmental -The aim of the study is to identify the genes that are differentially expressed during the grain development in wheat.-Study gene expression during the grain developmental Sample at 100 degree days, year 2004 and 2006 Sample at 200 degree days, year 2004 and 2006 Sample at 250 degree days, year 2004 and 2006 Sample at 300 degree days, year 2004 and 2006 Sample at 400 degree days, year 2004 and 2006
RNA-seq in grain unveils fate of neo- and paleopolyploidization events in bread wheat (Triticum aestivum L.).
No sample metadata fields
View SamplesEhf is a transcriptional regulator that is highly expressed and enriched in corneal epithelium. To gain insights into the role of Ehf in the corneal epithelium, we performed siRNA knockdown of Ehf in primary human corneal epithelial cells.
The Ets transcription factor EHF as a regulator of cornea epithelial cell identity.
Specimen part
View SamplesVascular adhesion protein-1 (VAP-1) is an endothelial cell-surface protein. It is also an enzyme posessing semicarbazide-sensitive amine oxidase activity (EC.1.4.3.6). VAP-1 is involved in leukocyte traffic. To study the role of VAP-1 in tumor immunity, we compared gene expression profiles in melanomas growing in VAP-1 -/- mice and their wid-type littermates.
Vascular adhesion protein-1 enhances tumor growth by supporting recruitment of Gr-1+CD11b+ myeloid cells into tumors.
No sample metadata fields
View Samples